NM_001387691.1:c.7C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001387691.1(POM121):​c.7C>T​(p.Pro3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000318 in 1,430,538 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 8 hom. )

Consequence

POM121
NM_001387691.1 missense

Scores

3
3
12

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28
Variant links:
Genes affected
POM121 (HGNC:19702): (POM121 transmembrane nucleoporin) This gene encodes a transmembrane protein that localizes to the inner nuclear membrane and forms a core component of the nuclear pore complex, which mediates transport to and from the nucleus. The encoded protein may anchor this complex to the nuclear envelope. There are multiple related genes and pseudogenes for this gene on chromosomes 5, 7, 15, and 22. Alternatively spliced transcript variants encoding different isoforms have been observed. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.007335216).
BP6
Variant 7-72925128-C-T is Benign according to our data. Variant chr7-72925128-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657544.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POM121NM_001387691.1 linkc.7C>T p.Pro3Ser missense_variant Exon 1 of 13 ENST00000434423.5 NP_001374620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POM121ENST00000434423.5 linkc.7C>T p.Pro3Ser missense_variant Exon 1 of 13 5 NM_001387691.1 ENSP00000405562.2 Q96HA1-1
POM121ENST00000395270.5 linkc.-151-1134C>T intron_variant Intron 4 of 15 1 ENSP00000378687.1 Q96HA1-3
POM121ENST00000627934.3 linkc.-151-1134C>T intron_variant Intron 3 of 14 5 ENSP00000486504.1 Q96HA1-2
ENSG00000272843ENST00000608799.1 linkn.-3G>A upstream_gene_variant 6

Frequencies

GnomAD3 genomes
AF:
0.000677
AC:
103
AN:
152120
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00511
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.000471
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00287
AC:
90
AN:
31354
Hom.:
3
AF XY:
0.00210
AC XY:
39
AN XY:
18590
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0159
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00151
Gnomad FIN exome
AF:
0.00108
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00108
GnomAD4 exome
AF:
0.000275
AC:
352
AN:
1278302
Hom.:
8
Cov.:
30
AF XY:
0.000268
AC XY:
168
AN XY:
627954
show subpopulations
Gnomad4 AFR exome
AF:
0.000241
Gnomad4 AMR exome
AF:
0.0138
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000343
Gnomad4 SAS exome
AF:
0.000895
Gnomad4 FIN exome
AF:
0.000641
Gnomad4 NFE exome
AF:
0.0000241
Gnomad4 OTH exome
AF:
0.000377
GnomAD4 genome
AF:
0.000677
AC:
103
AN:
152236
Hom.:
1
Cov.:
32
AF XY:
0.000766
AC XY:
57
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00510
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.000471
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000108
Hom.:
0
Bravo
AF:
0.00122
ExAC
AF:
0.000598
AC:
8

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Dec 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

POM121: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0070
T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.56
T
MetaRNN
Benign
0.0073
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.11
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.25
MutPred
0.13
Gain of phosphorylation at P3 (P = 0.0063);
MVP
0.13
ClinPred
0.22
T
GERP RS
3.8
Varity_R
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs559447703; hg19: chr7-72395666; API